ORESTES VICENTE FORLENZA
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Psiquiatria, Faculdade de Medicina - Docente
LIM/27 - Laboratório de Neurociências, Hospital das Clínicas, Faculdade de Medicina
LIM/27 - Laboratório de Neurociências, Hospital das Clínicas, Faculdade de Medicina
11 resultados
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- Lithium increases plasma brain-derived neurotrophic factor in acute bipolar mania: A preliminary 4-week study(2011) SOUSA, Rafael T. de; BILT, Martinus T. van de; DINIZ, Breno S.; LADEIRA, Rodolfo B.; PORTELA, Luis V.; SOUZA, Diogo O.; FORLENZA, Orestes V.; GATTAZ, Wagner F.; MACHADO-VIEIRA, RodrigoSeveral studies have suggested an important role for brain-derived neurotrophic factor (BDNF) in the pathophysiology and therapeutics of bipolar disorder (BPD). The mechanisms underlying the therapeutic effects of lithium in BPD seem to involve a direct regulation of neurotrophic cascades. However, no clinical study evaluated the specific effects of lithium on BDNF levels in subjects with BPD. This study aims to investigate the effects of lithium monotherapy on BDNF levels in acute mania. Ten subjects with bipolar I disorder in a manic episode were evaluated at baseline and after 28 days of lithium therapy. Changes in plasma BDNF levels and Young Mania Rating Scale (YMRS) scores were analyzed. A significant increase in plasma BDNF levels was observed after 28 days of therapy with lithium monotherapy (510.9 +/- 127.1 pg/mL) compared to pre-treatment (406.3 +/- 69.5 pg/mL) (p = 0.03). Although it was not found a significant association between BDNF levels and clinical improvement (YMRS), 87% of responders presented an increase in BDNF levels after treatment with lithium. These preliminary data showed lithium's direct effects on BDNF levels in bipolar mania, suggesting that short-term lithium treatment may activate neurotrophic cascades. Further studies with larger samples and longer period may confirm whether this biological effect is involved in the therapeutic efficacy of lithium in BPD.
- Platelet GSK3B activity in patients with late-life depression: Marker of depressive episode severity and cognitive impairment?(2011) DINIZ, Breno Satler; TALIB, Leda Leme; JOAQUIM, Helena Passarelli Giroud; PAULA, Vanessa Rodrigues Jesus de; GATTAZ, Wagner Farid; FORLENZA, Orestes VicenteObjective. Increased GSK3B activity has been reported as a state marker of major affective episodes in patients with depression and bipolar disorder. No study so far has addressed GSK3B activity in late-life depression. The aims of the present study were to determine GSK3B activity in platelets of elderly patients with major depression, and the association between GSK3B activity and the severity of depressive symptoms and cognitive impairment. Methods. Forty drug-free elderly patients with major depressive episode were compared to healthy older adults (n == 13). Severity of the depressive episode and current cognitive state were determined by the Hamilton Depression Scale (HAM-D) and the Cambridge Cognitive Test (CAMCOG), respectively. Total- and ser-9-phosphorylated GSK3B (tGSK3B and pGSK3B) were determined in platelets by enzyme immunometric assays (EIA). GSK3B activity was indirectly inferred by the GSK3B ratio (i.e. pGSK3B/tGSK3B). Results. Elderly depressed patients had significantly lower pGSK3B levels (P == 0.03) and GSK3B ratio (P == 0.03), indicating higher GSK3B activity. Higher GSK3B activity were observed in patients with severe depressive episode (HAM-D scores > 22, P == 0.03) and with cognitive impairment (CAMCOG scores < 86, P == 0.01). Conclusion. The present findings provide additional evidence of the involvement of GSK3B in the pathophysiology of late-life major depression. Higher GSK3B activity may be more relevant in those patients with more severe depressive symptoms and cognitive impairment.
- Current pharmacological approaches and perspectives in the treatment of geriatric mood disorders(2011) DINIZ, Breno S.; NUNES, Paula V.; MACHADO-VIEIRA, Rodrigo; FORLENZA, Orestes V.Purpose of review This work aims to review the most recent developments in the treatment of mood disorders (major depression and bipolar disorder) in the elderly. Recent findings In the last years, few new pharmacological interventions for mood disorders have been developed. Recent studies seek to provide alternative treatment strategies to achieve higher remission rates, including the association of antidepressants, mood stabilizers and psychotherapy and the treatment of specific clusters of symptoms, such as the adjunctive treatment of cognitive impairment with cholinesterase inhibitors. Also, recent studies have been assessing the potential of pharmacogenetic information in the prediction of treatment outcomes. Summary These factors altogether are expected to help the development of personalized treatment strategies that may improve outcomes with fewer adverse effects.
- Effects of a multidisciplinar cognitive rehabilitation program for patients with mild Alzheimer's disease(2011) VIOLA, Luciane F.; NUNES, Paula V.; YASSUDA, Monica S.; APRAHAMIAN, Ivan; SANTOS, Franklin S.; SANTOS, Glenda D.; BRUM, Paula S.; BORGES, Sheila M.; OLIVEIRA, Alexandra M.; CHAVES, Gisele F. S.; CIASCA, Eliane C.; FERREIRA, Rita C. R.; PAULA, Vanessa J. R. de; TAKEDA, Oswaldo H.; MIRANDEZ, Roberta M.; WATARI, Ricky; FALCAO, Deusivania V. S.; CACHIONI, Meire; FORLENZA, Orestes V.OBJECTIVE: To evaluate the effects of a multidisciplinary rehabilitation program on cognition, quality of life, and neuropsychiatric symptoms in patients with mild Alzheimer's disease. METHOD: The present study was a single-blind, controlled study that was conducted at a university-based day-hospital memory facility. The study included 25 Alzheimer's patients and their caregivers and involved a 12-week stimulation and psychoeducational program. The comparison group consisted of 16 Alzheimer's patients in waiting lists for future intervention. INTERVENTION: Group sessions were provided by a multiprofessional team and included memory training, computer-assisted cognitive stimulation, expressive activities (painting, verbal expression, writing), physiotherapy, and physical training. Treatment was administered twice a week during 6.5-h gatherings. MEASUREMENTS: The assessment battery comprised the following tests: Mini-Mental State Examination, Short Cognitive Test, Quality of Life in Alzheimer's disease, Neuropsychiatric Inventory, and Geriatric Depression Scale. Test scores were evaluated at baseline and the end of the study by raters who were blinded to the group assignments. RESULTS: Measurements of global cognitive function and performance on attention tasks indicated that patients in the experimental group remained stable, whereas controls displayed mild but significant worsening. The intervention was associated with reduced depression symptoms for patients and caregivers and decreased neuropsychiatric symptoms in Alzheimer's subjects. The treatment was also beneficial for the patients' quality of life. CONCLUSION: This multimodal rehabilitation program was associated with cognitive stability and significant improvements in the quality of life for Alzheimer's patients. We also observed a significant decrease in depressive symptoms and caregiver burden. These results support the notion that structured nonpharmacological interventions can yield adjunct and clinically relevant benefits in dementia treatment.
- Optimizing the CAMCOG test in the screening for mild cognitive impairment and incipient dementia: saving time with relevant domains(2011) APRAHAMIAN, Ivan; DINIZ, Breno Satler; IZBICKI, Rafael; RADANOVIC, Marcia; NUNES, Paula Villela; FORLENZA, Orestes VicenteObjective: To identify the CAMCOG sub-items that best contribute for the identification of patients with mild cognitive impairment (MCI) and incipient Alzheimer's disease (AD) in clinical practice. Methods: Cross-sectional assessment of 272 older adults (98 MCI, 82 AD, and 92 controls) with a standardized neuropsychological battery and the CAMCOG schedule. Backward logistic regression analysis with diagnosis (MCI and controls) as dependent variable and the sub-items of the CAMCOG as independent variable was carried out to determine the CAMCOG sub-items that predicted the diagnosis of MCI. Results: Lower scores on Language, Memory, Praxis, and Calculation CAMCOG sub-items were significantly associated with the diagnosis of MCI. A composite score obtained by the sum of these scores significantly discriminated MCI patients from comparison groups. This reduced version of the CAMCOG showed similar diagnostic accuracy than the original schedule for the identification of patients with MCI as compared to controls (AUC = 0.80 +/- 0.03 for the reduced CAMCOG; AUC = 0.79 +/- 0.03 for the original CAMCOG). Conclusion: This reduced version of the CAMCOG had similar diagnostic properties as the original CAMCOG and was faster and easier to administer, rendering it more suitable for the screening of subtle cognitive deficits in general clinical practice.
- Neurostructural predictors of Alzheimer's disease: A meta-analysis of VBM studies(2011) FERREIRA, Luiz K.; DINIZ, Breno S.; FORLENZA, Orestes V.; BUSATTO, Geraldo F.; ZANETTI, Marcus V.The identification of biological markers at early stages of Alzheimer's disease (AD) contributes to diagnostic accuracy and adds prognostic value. However, in spite of recent developments, results of neurostructural imaging studies on predicting conversion to AD are not uniform. We conducted a systematic review of voxel-based morphometry (VBM) studies about the neurostructural predictors of conversion to AD. Ten studies met inclusion criteria and nine reported baseline regional gray matter (GM) atrophy in mild cognitive impairment (MCI) or healthy subjects who progressed to AD. Using the method of Activation Likelihood Estimation, we meta-analyzed the coordinates from the six longitudinal VBM studies that enrolled subjects with amnestic MCI (aMCI) at baseline. These comprised a total of 429 aMCI subjects, of which 142 converted to AD. Meta-analysis yielded one significant cluster of GM volumetric reduction in aMCI patients who converted to AD, located in the left hippocampus and parahippocampal gyrus. In conclusion, left medial temporal lobe atrophy is the most consistent neurostructural biomarker to predict conversion from aMCI to AD.
- Understanding the neuroprotective mechanisms of lithium may have clinical significance Reply(2011) FORLENZA, Orestes V.; DINIZ, Breno S.; GATTAZ, Wagner F.
- Increased platelet GSK3B activity in patients with mild cognitive impairment and Alzheimer's disease(2011) FORLENZA, Orestes V.; TORRES, Carolina A.; TALIB, Leda L.; PAULA, Vanessa J. de; JOAQUIM, Helena P. G.; DINIZ, Breno S.; GATTAZ, Wagner F.The disruption of glycogen synthase kinase 3-beta (GSK3B) homeostasis has implications in the pathophysiology of neuropsychiatric disorders, namely Alzheimer's disease (AD). GSK3B activity is increased within the AD brain, favoring the hyperphosphorylation of microtubule-associated protein Tau and the formation of neurofibrillary tangles. Such abnormality has also been detected in leukocytes of patients with cognitive disorders. The aim of the present study was to determine the expression of total and phosphorylated GSK3B at protein level in platelets of older adults with varying degrees of cognitive impairment, and to compare GSK3B activity in patients with AD, mild cognitive impairment (MCI) and healthy controls. Sixty-nine older adults were included (24 patients with mild to moderate AD, 22 patients with amnestic MCI and 23 elderly controls). The expression of platelet GSK3B (total- and Ser-9 phosphorylated GSK3B) was determined by Western blot. GSK3B activity was indirectly assessed by means of the proportion between phospho-GSK3B to total GSK3B (GSK3B ratio), the former representing the inactive form of the enzyme. Ser-9 phosphorylated GSK3B was significantly reduced in patients with MCI and AD as compared to controls (p = 0.04). Platelet GSK3B ratio was significantly decreased in patients with MCI and AD (p = 0.04), and positively correlated with scores on memory tests (r = 0.298, p = 0.01). In conclusion, we corroborate previous evidence of increased GSK activity in peripheral tissues of patients with MCI and AD, and further propose that platelet GSK may be an alternative peripheral biomarker of this abnormality, provided samples are adequately handled in order to preclude platelet activation.
- The Alzheimer's Association external quality control program for cerebrospinal fluid biomarkers(2011) MATTSSON, Niklas; ANDREASSON, Ulf; PERSSON, Staffan; ARAI, Hiroyuki; BATISH, Sat Dev; BERNARDINI, Sergio; BOCCHIO-CHIAVETTO, Luisella; BLANKENSTEIN, Marinus A.; CARRILLO, Maria C.; CHALBOT, Sonia; COART, Els; CHIASSERINI, Davide; CUTLER, Neal; DAHLFORS, Gunilla; DULLER, Stefan; FAGAN, Anne M.; FORLENZA, Orestes; FRISONI, Giovanni B.; GALASKO, Douglas; GALIMBERTI, Daniela; HAMPEL, Harald; HANDBERG, Aase; HENEKA, Michael T.; HERSKOVITS, Adrianna Z.; HERUKKA, Sanna-Kaisa; HOLTZMAN, David M.; HUMPEL, Christian; HYMAN, Bradley T.; IQBAL, Khalid; JUCKER, Mathias; KAESER, Stephan A.; KAISER, Elmar; KAPAKI, Elisabeth; KIDD, Daniel; KLIVENYI, Peter; KNUDSEN, Cindy S.; KUMMER, Markus P.; LUI, James; LLADO, Albert; LEWCZUK, Piotr; LI, Qiao-Xin; MARTINS, Ralph; MASTERS, Colin; MCAULIFFE, John; MERCKEN, Marc; MOGHEKAR, Abhay; MOLINUEVO, Jose Luis; MONTINE, Thomas J.; NOWATZKE, William; O'BRIEN, Richard; OTTO, Markus; PARASKEVAS, George P.; PARNETTI, Lucilla; PETERSEN, Ronald C.; PRVULOVIC, David; REUS, Herman P. M. de; RISSMAN, Robert A.; SCARPINI, Elio; STEFANI, Alessandro; SOININEN, Hilkka; SCHROEDER, Johannes; SHAW, Leslie M.; SKINNINGSRUD, Anders; SKROGSTAD, Brith; SPREER, Annette; TALIB, Leda; TEUNISSEN, Charlotte; TROJANOWSKI, John Q.; TUMANI, Hayrettin; UMEK, Robert M.; BROECK, Bianca Van; VANDERSTICHELE, Hugo; VECSEI, Laszlo; VERBEEK, Marcel M.; WINDISCH, Manfred; ZHANG, Jing; ZETTERBERG, Henrik; BLENNOW, KajBackground: The cerebrospinal fluid (CSF) biomarkers amyloid beta (A beta)-42, total-tau (T-tau), and phosphorylated-tau (P-tau) demonstrate good diagnostic accuracy for Alzheimer's disease (AD). However, there are large variations in biomarker measurements between studies, and between and within laboratories. The Alzheimer's Association has initiated a global quality control program to estimate and monitor variability of measurements, quantify batch-to-batch assay variations, and identify sources of variability. In this article, we present the results from the first two rounds of the program. Methods: The program is open for laboratories using commercially available kits for A beta, T-tau, or P-tau. CSF samples (aliquots of pooled CSF) are sent for analysis several times a year from the Clinical Neurochemistry Laboratory at the Molndal campus of the University of Gothenburg, Sweden. Each round consists of three quality control samples. Results: Forty laboratories participated. Twenty-six used INNOTEST enzyme-linked immunosorbent assay kits, 14 used Luminex xMAP with the INNO-BIA AlzBio3 kit (both measure A beta-(1-42), P-tau(181P), and T-tau), and 5 used Mesa Scale Discovery with the A beta triplex (A beta N-42, A beta N-40, and A beta N-38) or T-tau kits. The total coefficients of variation between the laboratories were 13% to 36%. Five laboratories analyzed the samples six times on different occasions. Within-laboratory precisions differed considerably between biomarkers within individual laboratories. Conclusions: Measurements of CSF AD biomarkers show large between-laboratory variability, likely caused by factors related to analytical procedures and the analytical kits. Standardization of laboratory procedures and efforts by kit vendors to increase kit performance might lower variability, and will likely increase the usefulness of CSF AD biomarkers.
- Disease-modifying properties of long-term lithium treatment for amnestic mild cognitive impairment: randomised controlled trial(2011) FORLENZA, Orestes V.; DINIZ, Breno S.; RADANOVIC, Marcia; SANTOS, Franklin S.; TALIB, Leda L.; GATTAZ, Wagner F.Background Two recent clinical studies support the feasibility of trials to evaluate the disease-modifying properties of lithium in Alzheimer's disease, although no benefits were obtained from short-term treatment. Aims To evaluate the effect of long-term lithium treatment on cognitive and biological outcomes in people with amnestic mild cognitive impairment (aMCI). Method Forty-five participants with aMCI were randomised to receive lithium (0.25-0.5mmol/l) (n=24) or placebo (n = 21) in a 12-month, double-blind trial. Primary outcome measures were the modification of cognitive and functional test scores, and concentrations of cerebrospinal fluid (CSF) biomarkers (amyloid-beta peptide (A beta(42)), total tau (T-tau), phosphorylated-tau) (P-tau). Trial registration: NCT01055392. Results Lithium treatment was associated with a significant decrease in CSF concentrations of P-tau (P=0.03) and better perform-ance on the cognitive subscale of the Alzheimer's Disease Assessment Scale and in attention tasks. Overall tolerability of lithium was good and the adherence rate was 91%. Conclusions The present data support the notion that lithium has disease-modifying properties with potential clinical implications in the prevention of Alzheimer's disease.